Technical Field
The present invention belongs to the field of vaccines and medicaments for the prophylaxis and treatment of infectious diseases. In particular, it relates to inactivated viruses useful as vaccine or medicament for preventing or treating viremia, the transmission and clinical symptoms, in particular malformations in newborn ruminants such as cattle, sheep and goats, induced by Schmallenberg virus.
Background Information
A novel orthobunyavirus, the Schmallenberg virus (SBV), was discovered in Europe in November 2011. After the first detection, the reported cases of SBV in sheep, cattle, and goats dramatically accumulated in several European countries to several thousand cases of PCR-positive malformed lambs and calves (1, 2). The virus was detected by metagenomics at the Friedrich-Loeffler-Institut (FLI) in samples of cattle with milk drop and fever. The investigated samples were collected in a farm near the city of Schmallenberg (North Rhine-Westphalia, Germany), and consequently the virus was named Schmallenberg virus (SBV). SBV is a member of the genus Orthobunyavirus within the family Bunyaviridae. It is related to the so-called Simbu serogroup viruses (1).
Orthobunyaviruses have a segmented, negative stranded RNA genome and are mainly transmitted by insect vectors like midges and mosquitos. The three segments (S, M and L) of the Orthobunyavirus genome allow genetic reassortment, which naturally occurs resulting in the emergence of viruses with new biological properties (3). The largest segment L encodes the RNA-dependent RNA polymerase. The M-segments encodes the viral surface glycoproteins Gn and Gc which are responsible for cell fusion, viral attachment and the induction of neutralizing antibodies. The small S-segment encodes the nucleocapsid N which is also involved in complement fixation (4). The relationship between Orthobunyaviruses was often only determined by serological cross-reactivity (5). In the era of DNA sequencing, phylogenetics has additionally been assessed by comparison of partial genome sequences (full N and partial Gc gene) (6). Therefore, available and published genome sequence information of full-length genomes is sparse. As a consequence, in-depth phylogenetic analyses are difficult. In conclusion, a detailed and reliable taxonomic classification of SBV could not be made. Preliminary investigations showed similarities of the M- and L-segment sequences to partial AKAV and Aino virus (AINOV) sequences. The N gene was most closely related to Shamonda virus (SHAV) (1).
SBV is like Akabane virus (AKAV) able to cross the placental barrier in pregnant cows and sheep, infect the fetus and cause fatal congenital defects during a susceptible stage in pregnancy (2). The Simbu serogroup, named after the prototype virus, is the largest serogroup of Orthobunyavirus and contains at least 25 viruses, among them medically important viruses such as Akabane virus, Oropouche virus, Sathuperi virus or Douglas virus, most of which can cause malformations in new born ruminants, but also human beings can be affected. Akabane virus, for instance, causes congenital defects in ruminants and circulates in Asia, Oceania and Africa, whereas Oropouche virus is responsible for large epidemics of Oropouche fever, a zoonosis similar to dengue fever, in human populations in South America. Sathuperi virus has lent his name to the Sathuperi serogroup, to which belong also Douglas virus and SBV.
SBV was the first orthobunyavirus of the Simbu serogroup detected in Europe. The virus is apparently transmitted by arthropod vectors. Biting midges probably play an important role in transmission. According to the current state of knowledge, ruminants are susceptible to infection with SBV. Adult animals may develop mild disease, if any. However, transplacental infection occurs frequently and can lead to severe congenital malformation of the vertebral column (Kyphosis, lordosis, scoliosis, torticollis) and of the scull (macrocephaly, brachygnathia inferior) as well as variable malformations of the brain (hydracephaly, porencephaly, cerebellar hypoplasia, hypoplasia of the brain stem) and of the spinal cord in lambs, kids and calves. The infection spread rapidly over large parts of North Western Europe. Belgium, Germany, France, Italy, Luxembourg, the Netherlands, Spain and the United Kingdom have been affected so far.
Therefore, SBV is a serious threat to ruminant livestock in Europe since vaccines are currently not available.
Thus, there is a strong need for vaccines and medications effecting a rapid induction of neutralizing antibodies for the prophylaxis and treatment of Schmallenberg virus infection.